ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6127A>G (p.Lys2043Glu)

dbSNP: rs2137524563
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001883393 SCV002140810 uncertain significance Hereditary breast ovarian cancer syndrome 2021-08-29 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 2043 of the BRCA2 protein (p.Lys2043Glu). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. This variant has not been reported in the literature in individuals affected with BRCA2-related conditions.
University of Washington Department of Laboratory Medicine, University of Washington RCV003159047 SCV003850960 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Ambry Genetics RCV003159047 SCV005102211 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-01 criteria provided, single submitter clinical testing The p.K2043E variant (also known as c.6127A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 6127. The lysine at codon 2043 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, glutamic acid is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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